{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T05:18:28Z","timestamp":1791695908210,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP25fk0310529"],"award-info":[{"award-number":["JP25fk0310529"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP25fk0210174"],"award-info":[{"award-number":["JP25fk0210174"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI Grant-in-Aid for Scientific Research","doi-asserted-by":"publisher","award":["JP25K11170"],"award-info":[{"award-number":["JP25K11170"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Chronic hepatitis B virus (HBV) infection is a major risk factor of hepatocellular carcinoma (HCC), and hepatocyte-derived host factors play important roles in HBV-associated tumor progression. Alpha-1B glycoprotein (A1BG) is a plasma glycoprotein reported to be dysregulated in multiple cancers. In this study, we investigated the functional role of A1BG in HBV-associated HCC progression. Methods: Both the HepG2 and HBV-transfected HepG2 cell lines were used to examine the biological effects of A1BG. A1BG expression was modulated using siRNA and a plasmid vector. A series of functional assays were conducted to assess cell proliferation, apoptosis, stemness, migration, and invasion. RNA microarray analysis and gene set enrichment analysis (GSEA) were performed to identify A1BG-regulated pathways. Results: Functionally, A1BG overexpression suppressed cell proliferation, stemness, migration, invasion, and HBV products while promoting apoptosis in both HepG2 and HBV-transfected HepG2 cells. In contrast, opposite effects were shown in the event of A1BG knockdown. Moreover, A1BG expression was reduced in HBV-associated HCC tissues and correlated with advanced pathological stage and poor prognosis. RNA microarray analysis and GSEA revealed the activation of anti-HBV-related genes and suppression of FGFR1 signaling and the matrix metalloproteinase pathway in A1BG-overexpressing cells. Conclusions: This study provides evidence that A1BG may be a novel host factor associated with the in vitro suppression of HBV replication and HCC progression by modulating pathways related to enhanced antiviral effects, reduced proliferative capacity and stemness, and suppression of EMT. These findings suggest that A1BG is a potential therapeutic target in HBV-related HCC.<\/jats:p>","DOI":"10.3390\/cancers18040662","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:50:30Z","timestamp":1771401030000},"page":"662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alpha-1B Glycoprotein Is a Novel Hepatocyte-Derived Host Factor Associated with In Vitro Inhibition of HBV Replication and Hepatocellular Carcinoma Progression"],"prefix":"10.3390","volume":"18","author":[{"given":"Juan","family":"Lyu","sequence":"first","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"},{"name":"Department of Clinical Laboratory, Shaoxing People\u2019s Hospital, Shaoxing 312000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1929-7305","authenticated-orcid":false,"given":"Takuto","family":"Nosaka","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Murata","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Akazawa","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5768-3805","authenticated-orcid":false,"given":"Tomoko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5472-8193","authenticated-orcid":false,"given":"Tatsushi","family":"Naito","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shaoxing People\u2019s Hospital, Shaoxing 312000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3160-3555","authenticated-orcid":false,"given":"Yasunari","family":"Nakamoto","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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